Introducing Targeting Units or pH-Releasable Immunodrugs into Core-Clickable Nanogels

Heck, Alina G.; Schwiertz, David; Lantzberg, Bellinda; Nguyen, Ha-Chi; Forster, Robert; Scherger, Maximilian; Opatz, Till; Van Ginderachter, Jo A.; Nuhn, Lutz

doi:10.1016/j.eurpolymj.2024.113150

Cited by 3 publications

(2 citation statements)

References 58 publications

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“…S13‡). In analogy to our previous studies, 17 the reaction with the secondary amine-bearing fluorescent dye 4-nitro-7-piperazino-2,1,3-benzoxadiazole (NBD-PZ, Fig. S10–S12‡) resulted in a pH-reversible conjugation to the linker system (Fig.…”

Section: Resultssupporting

confidence: 62%

“…By carefully choosing the bifunctional 2-propionic-3-methylmaleic anhydride linker with an additional azide group for bioorthogonal click chemistry, we recently verified that a pH-sensitive release can only be guaranteed for secondary amines, but not for primary amines, and we subsequently applied it for nanogel-mediated endosomal immunodrug delivery. 17 In this study, we now aimed at further investigating the pH reversibility of the anhydride system for primary amines and were successfully able to restore it for aliphatic amines, depending on the reaction solvent during the fabrication process. When treated with fluorescent dyes bearing primary amines in DMSO, the bifunctional linker forms the corresponding imide systems, whereas functionalization in diethyl ether avouches the formation of regioisomer amides that can get released upon acidification.…”

Section: Introductionmentioning

confidence: 99%

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Restoring the pH-responsiveness for amine-conjugated 2-propionic-3-methylmaleic anhydride linkers

Heck,

Nuhn

2024

Org. Chem. Front.

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Section: Resultssupporting

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Restoring the pH-responsiveness for amine-conjugated 2-propionic-3-methylmaleic anhydride linkers

Heck,

Nuhn

2024

Org. Chem. Front.

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PH‐Triggered, Lymph Node Focused Immunodrug Release by Polymeric 2‐Propionic‐3‐Methyl‐maleic Anhydrides with Cholesteryl End Groups

Heck,

Medina‐Montano,

Zhong

et al. 2024

Adv Healthcare Materials

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Gaining spatial control over innate immune activation is of great relevance during vaccine delivery and anticancer therapy, where one aims at activating immune cells at draining lymphoid tissue while avoiding systemic off‐target innate immune activation. Lipid‐polymer amphiphiles show high tendency to drain to lymphoid tissue upon local administration. Here, pH‐sensitive, cholesteryl end group functionalized polymers as stimuli‐responsive carriers are introduced for controlled immunoactivation of draining lymph nodes. Methacrylamide‐based monomers bearing pendant 2‐propionic‐3‐methylmaleic anhydride groups are polymerized by Reversible Addition‐Fragmentation Chain Transfer (RAFT) polymerization using a cholesterol chain‐transfer agent (chol‐CTA). The amine‐reactive anhydrides are conjugated with various amines, however, while primary amines afforded irreversible imides, secondary amines provided pH‐responsive conjugates that are released upon acidification. This can be applied to fluorescent dyes for irreversibly carrier labeling or immunostimulatory Toll‐like receptor (TLR) 7/8 agonists as cargos for pH‐responsive delivery. Hydrophilization of remaining anhydride repeating units with short PEG‐chains yielded cholesteryl‐polymer amphiphiles that showed efficient cellular uptake and increased drug release at endosomal pH. Moreover, reversibly conjugated TLR 7/8 agonist amphiphiles efficiently drained to lymph nodes and increased the number of effectively maturated antigen‐presenting cells after subcutaneous injection in vivo. Consequently, cholesteryl‐linked methacrylamide‐based polymers with pH‐sensitive 2‐propionic‐3‐methylmaleic anhydride side groups provide ideal features for immunodrug delivery.

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Nonconventional Luminogens Based on Poly(methyl vinyl ether maleic anhydride) and 4-(2-Aminoethyl)morpholine for Mg²⁺ Detection and Targeting Lysosomes

He,

Liu,

et al. 2024

ACS Appl. Polym. Mater.

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Compared with traditional luminescent materials, nonconventional luminogens have been extensively studied due to their unique properties and wide range of applications. However, the study of nonconventional luminescent polymers is rare because most luminescent polymeric materials can only emit light at high concentrations and require noble metal catalysts for synthesis. Particularly, their application in the field of metal ion detection and biological imaging is still restricted. To expand its application scope, this work designed a series of luminescent polymeric materials only containing carboxyl and amide groups, which were synthesized from poly(methyl vinyl ether maleic anhydride) and 4-(2-aminoethyl)morpholine at different molar ratios (PMVEMA/AML are 1:1, 1:2, and 1:3). The synthesized luminogens exhibited controllable luminescence colors and excellent solubility in various commonly used solvents. Additionally, the polymers can achieve luminescence in dilute solutions, and the maximal luminescence efficiencies can be up to 5.55%. At last, polymer M3 with good biocompatibility and low cytotoxicity can be used to sensitively detect Mg 2+ ions in vivo and in vitro. Notably, polymer M3 possesses the ability to target the organelle lysosome in cell imaging.

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Introducing Targeting Units or pH-Releasable Immunodrugs into Core-Clickable Nanogels

Cited by 3 publications

References 58 publications

Restoring the pH-responsiveness for amine-conjugated 2-propionic-3-methylmaleic anhydride linkers

Restoring the pH-responsiveness for amine-conjugated 2-propionic-3-methylmaleic anhydride linkers

PH‐Triggered, Lymph Node Focused Immunodrug Release by Polymeric 2‐Propionic‐3‐Methyl‐maleic Anhydrides with Cholesteryl End Groups

Nonconventional Luminogens Based on Poly(methyl vinyl ether maleic anhydride) and 4-(2-Aminoethyl)morpholine for Mg²⁺ Detection and Targeting Lysosomes

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Introducing Targeting Units or pH-Releasable Immunodrugs into Core-Clickable Nanogels

Cited by 3 publications

References 58 publications

Restoring the pH-responsiveness for amine-conjugated 2-propionic-3-methylmaleic anhydride linkers

Restoring the pH-responsiveness for amine-conjugated 2-propionic-3-methylmaleic anhydride linkers

PH‐Triggered, Lymph Node Focused Immunodrug Release by Polymeric 2‐Propionic‐3‐Methyl‐maleic Anhydrides with Cholesteryl End Groups

Nonconventional Luminogens Based on Poly(methyl vinyl ether maleic anhydride) and 4-(2-Aminoethyl)morpholine for Mg2+ Detection and Targeting Lysosomes

Contact Info

Product

Resources

About

Nonconventional Luminogens Based on Poly(methyl vinyl ether maleic anhydride) and 4-(2-Aminoethyl)morpholine for Mg²⁺ Detection and Targeting Lysosomes